固態栽培樟芝防治癌症之重要機轉-癌症逆轉

Cancer reversion as a character of solid state cultivated Cancer reversion as a character of solid state cultivated Taiwanofungus camphoratus for cancer prevention

陳佳鈺(Chia-Yu Chen)

指導教授 ： 鄧文炳

臺北醫學大學/口腔學院/生物醫學材料研究所/碩士(2005年)

摘要

中文摘要 根據研究發現癌症是可以逆轉的，以感染病毒或以化學物質處理或與放射線接觸等方式藉著啟動腫瘤細胞中之逆轉作用機制，讓癌細胞不表現腫瘤特性，甚至於恢復成相當程度之正常細胞。所謂癌症逆轉現象(Cancer Reversion)，意指腫瘤細胞回復「部分正常」，而成為不具威脅性地可與人體共存的人癌共生現象。 本實驗室已經建立了可供癌症逆轉機制探討的研究模式。樟芝﹐又稱牛樟芝或牛樟菇，是台灣特有的真菌，因無法以人工栽培，因此更顯得珍貴。以其中的多醣體(Polysccharides)、三?類(Triterpenoids)及超氧歧化酵素(Superoxide Dismutase)為主要的研究份。根據初步研究樟芝有明顯的抑制腫瘤細胞生長及抑制癌病毒作用的效果，且以樟芝進行細胞試驗，結果顯示樟芝具有癌症逆轉的特性。 具腫瘤誘發性的HeLa細胞的表面抗原，其具有自磷酸化(Autophosphorylation)活性，是一種細胞的腸鹼性磷酸酵素(Intestinal alkaline phosphatase, IAP)，因此本實驗室嘗試解析IAP表現與腫瘤誘發性之間的關係。實驗結果發現樟芝能夠抑制腫瘤細胞內鹼性磷酸酵素的表現。此外在基因層面的探討，初步實驗結果發現， 樟芝有增強抑癌基因p53表現的趨勢；而對子宮頸癌主要的E6/E7致病因子則有抑制的功效。在動物實驗方面，餵食樟芝對於腫瘤細胞生長確實有抑制的效果。以流式細胞儀技術分析樟芝對癌細胞的影響，可能並非走細胞毒殺的路徑，因此可以更加的推斷藥物對細胞的作用是進行癌症逆轉的模式。 關鍵字：癌症逆轉、子宮頸癌細胞、腸鹼性磷酸酵素(IAP)、致癌基因E6/E7、抑癌基因p53、樟芝

關鍵字

癌症逆轉 ； 子宮頸癌細胞 ； 腸鹼性磷酸酵素(IAP) ； 致癌基因E6/E7 ； 抑癌基因p53 ； 樟芝

並列摘要

Abstract Neoplastic transformation of normal cells can occur spontaneously or can be induced by viruses, chemical carcinogens, or irradiation. Such transformed cells; however, can also spontaneously, or be induced to, lose some of their tumorgenic characteristics and revert back to a more normal phenotypic state through correction of malignant behavior by microenvironmental cues. It has been suggested that the frequency of cell reversion to the non-tumorigenic phenotype is much higher than re-reversion to the tumorigenic phenotype, and that the reversion is paralleled by a regulation in malignant behavior and tumorigenicity. Such reversion may be a consequence of both genetic and epigenetic processes. One of the most challenging goals of cancer therapy is to exploit the potential of such reversion. Meeting this goal requires the identification of agent(s) with the ability to arrest tumor growth while having minimal effect on normal tissue. Taiwanofungus camphoratus, known as Niu-Chang-Chih or Niu-Chang-Ku, is rare and expensive. It growths only on the inner heartwood wall of the endemic evergreen Cinnamonum kanehirai and is not easily cultivated. The main ingredients of the fruit body includes: Polysaccharides; Triterpenoids and Superoxide dimutase(SOD). Traditionally, it is used as a Chinese remedy for food, alcohol, and drug intoxication, diarrhea, abdominal pain, hypertension, skin itches, and liver cancer. Concentrated ethanol extract of fruiting bodies of Taiwanofungus camphoratus exhibited immunomodulating effects in human leukocytes; exited antioxidant effects, and induced apoptosis in cultured human premyelocytic leukemia HL-60 cells. In addition Taiwanofungus camphoratus polysaccharides exhibit anti-hepatitis B virus effects. The expression of the HeLa tumor-associated marker, intestinal alkaline phosphatase (IAP), has been shown to be necessary but not sufficient to confer the tumorigenic phenotype on Hela x skin fibroblast human hybrid cells. We have previously used the loss of IAP activity and expression to investigate the reversion of a UVC-induced tumorigenic HeLa x skin fibroblast human hybrid cell line to the non-tumorigenic phenotype. Now, we describe for the first time a series of observations on the reversion of tumorigenic HeLa cervical carcinoma cells by Taiwanofungus camphoratus to a much less aggressive tumorigenic phenotype. This reversion was associated with the down-regulation of E6/E7 oncoproteins at the transcriptional level and subsequent reactivation of p53. Key words: Cancer Reversion, IAP, E6/E7, p53, HeLa cell, Taiwanofungus camphoratus

並列關鍵字

Cancer Reversion ； IAP ； E6/E7 ； p53 ； HeLa cell ； Taiwanofungus camphoratus

參考文獻

54. 陳勁初,陳清農,許勝傑,黃仕政,陳炎鍊. 台灣特有真菌-樟芝菌絲體之開發. Fung.Sci. 16: 7-22, 2001.

67. SH Lin, I CC, CN Weng, CM Chen. Effects of a Chinese Herbal Medicine Yigan Kang on TEGV Infectivity in Tissue Culture. J.Chinese Society of Veterinary Science. 26: 110-116, 2000.

1. Tamaki T, Naomoto Y, Kimura S, Kawashima R, Shirakawa Y, Shigemitsu K, Yamatsuji T, Haisa M, Gunduz M, Tanaka N. Apoptosis in normal tissues induced by anti-cancer drugs. J.Int.Med.Res. 31: 6-16, 2003.

2. Yano H, Mizoguchi A, Fukuda K, Haramaki M, Ogasawara S, Momosaki S, Kojiro M. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res. 54: 448-454, 1994.

3. Kao ST, Yeh CC, Hsie CC, Yang MD, Lee MR, Liu HS, Lin JG. The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest. Life Sci. 69: 1485-1496, 2001.